Process for the preparation of halogenated aromatic primary amines

ABSTRACT

The catalytic hydrogenation of halogenated nitro aromatics using Raney nickel in the presence of a formamidine salt as dehalogenation inhibitor affords halogenated aromatic primary amines in high yields and high chemical purity within short reaction times even at elevated temperatures.

The invention relates to a process for the preparation of halogenatedaromatic primary amines by catalytic hydrogenation of halogenatedaromatic nitro compounds in the presence of Raney nickel and aformamidine salt as dehalogenation inhibitor.

It is known that halogenated aromatic primary amines are obtained bycatalytic hydrogenation of halogenated aromatic nitro compounds. Thehydrogenation additionally leads to a dehalogenation and thus tomixtures of halogen-free and halogenated aromatic primary amines whichare difficult to separate.

DE-AS No. 2,441,650 describes a hydrogenation process in the presence ofRaney nickel in which dicyanodiamide, cyanamide or calcium cyanamide isused as dehalogenation inhibitor. It is also disclosed that thedicyanodiamide is partially hydrogenated. However, since the reactionmixture is basic, no formamidine salt can be formed as a stableintermediate. The reason is that, as G. Trumpler et al. alreadydescribed in Helv. Chim. Acta, 39, p. 407-416 (1959), in the catalytichydrogenation of cyanamide using Raney nickel, formamidine salts areonly formed as primary reaction products under weakly acidic conditions(pH≈6).

It has now been found that formamidine salts suppress dehalogenationduring the hydrogenation of halogenated aromatic nitro compounds even atelevated temperatures in an efficient manner. The desired halogenatedaromatic amines are obtained in higher, under favourable conditions invirtually quantitative, yields compared to those obtained in thereaction without additives, and the percentage of byproducts can besubstantially below 1% by weight under optimum conditions. The catalystactivity is not impaired so that the Raney nickel can be usedrepeatedly. The hydrogenation rate is not affected significantly. Theprocess is suitable for being carried out on an industrial scale.

The invention relates to a process for the preparation of halogenatedaromatic primary amines by catalytic hydrogenation of halogenatedaromatic nitro compounds in the presence of Raney nickel at a pressureof 0.1 to 100 bar and at a temperature of 30° to 150° C. in an inertsolvent and in the presence of an inhibitor against dehalogenation,wherein the inhibitor is a formamidine salt.

Examples of suitable nitro compounds are those of the general formula

    (Y).sbsb.xA-NO.sub.2).sbsb.y

in which x and y, independently of one another, are a number from 1 to6, preferably 1 to 3 and in particular 1 or 2, Y is halogen, inparticular F, Cl and Br and A is an aromatic radical having 6 to 18carbon atoms which can additionally contain further substituents. Y isin particular Cl or Br.

The aromatic radical preferably contains 6 to 14, in particular 6-10,carbon atoms and represents in particular an aromatic hydrocarbonradical. Examples of aromatic hydrocarbons from which the radical can bederived are, for example: benzene, naphthalene, phenanthrene, biphenyl,indane, benzene linked by bridging groups Y¹ stable to hydrogenation,for example ##STR1## in which Y¹ can be C₁ -C₄ alkylene, C₁ -C₆alkylidene, --O--, --S--, --SO₂ -- or --CO--.

Further examples of suitable substituents for the radical A are C₁ -C₄alkyl, C₁ -C₄ halogenoalkyl, C₁ -C₄ alkoxy, C₁ -C₄ halogenoalkoxy or C₁-C₄ alkylthio, C₅ cycloalkyl or C₆ cycloalkyl, cyano, hydroxyl, C₁ -C₈acyl or C₁ -C₈ acyloxy, --COOH, --SO₃ H, --COOM and --SO₃ M where M isan alkali metal cation, for example Na⁺ or is ammonium, --SO₃ R³ or CO₂R³ where R³ is C₁ -C₆ alkyl, phenyl or benzyl, --NH₂, C₁ -C₈ alkyl or C₁-C₈ dialkylamino, C₁ -C₈ acylamino or C₁ -C₈ aminocarbonyl. A fewexamples are methyl, ethyl, n-propyl or isopropyl, n-butyl, i-butyl ort-butyl, methyloxy, ethyloxy, chloroethyloxy, methylthio, chloromethyl,fluoromethyl, trifluoromethyl, trichloromethyl, cyclopentyl, cyclohexyl,acetyl, propionyl, acetyloxy, methoxysulfonyl, methoxycarbonyl orethoxycarbonyl, methylamino, dimethylamino, acetylamino, aminocarbonyland dimethylaminocarbonyl.

Examples of nitro compounds are o-, m- and p-chloro or-bromo-nitrobenzene, 2,3-, 3,4-, 2,4-, 2,6-, 3,5- and 2,5-dichloro- or-dibromonitrobenzene, 2,3,4- and 2,3,5- trichloronitrobenzene,2-chloro-3-bromonitrobenzene, 1-chloro or 1-bromo-2,4-dinitrobenzene,3,4-dichloro-1,6-dinitrobenzene, 2,4-dichloro-1,6-dinitrobenzene,1-chloro-2,4,6-trinitrobenzene, 4- or 6-chloro-1-methyl-2-nitrobenzene,2- or 6-bromo-1-methyl-4-nitrobenzene, 4- or6-chloro-1-ethyl-2-nitrobenzene, 2- or 3-bromo-1-ethyl-4-nitrobenzene,4- or 6-chloro-1-methoxy-4-nitrobenzene, 4- or 6-chloro-2-nitrophenol,1-chloro- or 1-bromo-2-nitronaphthalene, 1-chloro- or1-bromo-2,7-dinitronaphthalene, 2-chloro-4-nitrodiphenyl,2,2'-dichloro-4,4'-dinitrodiphenyl, 2-bromo-4,4'-dinitrobenzophenone,bis(3,3'-dichloro-4,4'-dinitrophenyl)methane and3,3'-dichloro-4,4'-dinitrodiphenyl ether.

The formamidine salt is advantageously used in an amount of 0.1 to 30mol % preferably 0.1 to 20 mol % and in particular 0.5 to 15 mol %,relative to the nitro compound.

The formamidine cation can be substituted by one, two or threehydrocarbon radicals which contain preferably 1 to 18, particularly1--12, and especially 1 to 6, carbon atoms. The anion of the formamidinesalt can be derived, for example, from aliphatic or aromatic carboxylicacids, preferably mono- or dicarboxylic acids containing preferably 1 to18, particularly 1-8, and especially 1 to 4, carbon atoms.

A preferred embodiment is that in which the formamidine salt conforms tothe formula I ##STR2## in which R¹, R² and R³, independently of oneanother, are H, or linear or branched C₁ -C₁₂ alkyl, C₅ cycloalkyl or C₆cycloalkyl, C₆ -C₁₈ alkylcycloalkyl, C₆ -C₁₀ cycloalkylalkyl, C₇ C₁₈alkylcycloalkylalkyl, where the cycloalkyl contains 5 or 6 ring carbonatoms, C₆ -C₁₀ aryl, C₇ -C₁₈ alkaryl, C₇ -C₁₂ aralkyl or C₇ -C₁₈alkaralkyl or R¹ and R² together are tetramethylene or pentamethylene or3-oxa-1,5-pentylene, X is the anion of an acid, in particular of a C₁-C₁₈ mono- or -dicarboxylic acid, and n is 1 or 2.

R¹, R² and R³ as alkyl contain preferably 1 to 6 and in particular 1 to4 carbon atoms. Examples are methyl, ethyl and the isomers of propyl,butyl, pentyl, hexyl, heptyl, octyl, decyl and dodecyl. R¹, R² and R³ ascycloalkyl are, for example, cyclopentyl and cyclohexyl. R¹, R² and R³as alkylcycloalkyl preferably contain 6 to 12, in particular 6 to 10,carbon atoms. Examples are methylcyclopentyl, methylcyclohexyl,ethylcyclohexyl and n-propylcyclohexyl. R¹, R² and R³ as cycloalkylalkylare in particular cyclopentylmethyl or cyclohexylmethyl. R¹, R² and R³as alkylcycloalkylalkyl contain preferably 7 to 12 carbon atoms and arein particular C₁ -C₄ alkylcyclopentylmethyl or C₁ -C₄alkylcyclohexylmethyl. R¹, R² and R³ having the meaning of aryl can be,for example, naphthyl and in particular phenyl. In the aryl-containingradicals for R¹, R² and R³, aryl is in particular phenyl. R¹, R² and R³having the meaning of alkaryl preferably contain 7 to 12 carbon atomsand are in particular C₁ -C₄ alkylphenyl. R¹, R² and R³ as aralkyl arein particular benzyl and phenylethyl. R¹, R² and R³ as alkaralkylpreferably contain 8 to 14 carbon atoms and are in particular C₁ -C₄alkylbenzyl.

R¹, R² and R³ are preferably H or aliphatic or cycloaliphatic radicals.

In a preferred embodiment, R¹, R² and R³, independently of one another,are H or C₁ -C₈ alkyl, in particular H, methyl or ethyl and especiallythey are each H.

In formula I, n is preferably 1.

X as the anion of a mono- or dicarboxylic acid preferably contains 1-18,particularly 1-12 and in particular 1 to 8 carbon atoms. They can bealiphatic or aromatic carboxylic acids which can conform, for example,to the formulae

    R.sup.4 COOH or R.sup.5 (COOH).sub.2

in which R⁴ is linear or branched alkyl having particularly 1 to 6carbon atoms or is cyclohexyl, phenyl or benzyl, and R⁵ is a directbond, linear or branched C₂ -C₆ alkylene or cyclohexylene or phenylene.In particular, X in formula I represents the anion of an aliphatic mono-or dicarboxylic acid having preferably 1 to 4 carbon atoms.Particularly, X represents the anions (COO)₂ ²⊖, HCOO.sup.⊖, CH₃COO.sup.⊖, CH₃ CH₂ COO.sup.⊖, CH₃ CH₂ CH₂ COO.sup.⊖ or CH₂ (COO)₂ ²⊖,and very particularly CH₃ COO.sup.⊖.

The formamidine salt is in particular formamidine acetate.

The formamidine salt can be added to the reaction mixture as such or canbe generated in situ by a known method before the hydrogenation, forexample by hydrogenating a substituted or unsubstituted cyanamide in thepresence of Raney nickel and an acid.

The in situ formation of the substituted or unsubstituted formamidinesalt takes place at such a high rate that this reaction can be carriedout in the presence of a halogenated aromatic nitro compound. In thisreaction, some of the nitro compound can be added and the remainder canbe metered in, or the total amount of nitro compound can be introducedinitially as well.

The amount of Raney nickel is preferably 0.5 to 20% by weight,particularly 1 to 10% by weight, relative to the nitro compound.

The hydrogenation is carried out without solvent or in an inert solvent.Examples of suitable solvents are alkanols (methanol, ethanol, propanol,butanol, methoxyethanol or ethoxyethanol), ethers (dibutyl ether,t-butyl methyl ether, tetrahydrofuran, dioxane, ethylene glycol dimethylether, diethylene glycol dimethyl ether), amides and lactams(dimethylformamide, dimethylacetamide, N-methylpyrrolidone), esters andlactones (ethyl acetate, γ-butyrolactone), hydrocarbons (pentane,hexane, methylcyclohexane, benzene, toluene, xylene, chlorobenzene), andwater. In the hydrogenation without solvent, the halogenated aromaticamine resulting in the hydrogenation is the solvent.

In a preferred embodiment, the solvent used is a C₁ -C₄ alkanol byitself or in a mixture with water. In particular, methanol is used.

The reaction temperature is advantageously 50° to 120° C. The pressureis preferably 1 to 30 bar. The reaction time depends mainly on thereaction conditions and is in general less than two hours.

The process according to the invention can be carried out in such amanner that the nitro compound, the Raney nickel, the solvent and theformamidine salt is introduced into an autoclave and the air is firstdisplaced by nitrogen which is then displaced by hydrogen. The autoclaveis then sealed, hydrogen is injected until the desired pressure isreached, and the mixture is heated to the reaction temperature. Afterthe reaction is completed, the reaction mixture is separated off fromthe catalyst. The reaction product can then be freed from the water ofreaction and solvent and be further purified by distillation orrecrystallization. As is known, the primary aromatic amines areintermediates for the preparation of dyes.

The examples which follow illustrate the invention in more detail.

EXAMPLE 1

40.8 g of 1-chloro-2,4-dinitrobenzene, 2 g of Raney nickel (60%,aqueous), 1.5 g of formamidine acetate and 120 ml of methanol areintroduced in an autoclave equipped with gas introduction stirrer. Theair in the autoclave is then displaced by nitrogen and then by hydrogen.The hydrogenation is carried out at a pressure of 10 bar and atemperature of 60° C. The hydrogenation time is 11/4 hours.1-Chloro-2,4-diaminobenzene, 99% pure (analysed as1-Chloro-2,4-acetamidobenzene by liquid chromatography), is obtained inquantitative yield.

EXAMPLE 2

39.8 g of 1-chloro-2-nitrobenzene, 2 g of Raney nickel (60%, aqueous),1.5 g of formamidine acetate and 120 ml of methanol are introduced in anautoclave equipped with gas introduction stirrer. The air in theautoclave is then displaced by nitrogen and then by hydrogen. Thehydrogenation is carried out at a pressure of 10 bar and a temperatureof 90° C. The hydrogenation time is 11/2hours. 1-Chloro-2-aminobenzene,99.4% pure (analysed by gas chromatography), is obtained in quantitativeyield.

EXAMPLE 3

39.8 g of 1-chloro4-nitrobenzene, 2 g of Raney nickel (60%, aqueous),1.5 g of formamidine acetate and 120 ml of methanol are introduced in anautoclave equipped with gas introduction stirrer. The air in theautoclave is then displaced by nitrogen and then by hydrogen. Thehydrogenation is carried out at a pressure of 12 bar and a temperatureof 80° C. The hydrogenation time is 11/2 hours. 1-Chloro-4-aminobenzene,99.7% pure (analysed by gas chromatography), is obtained in quantitativeyield.

EXAMPLE 4

39.8 g of 1-chloro-3-nitrobenzene, 2 g of Raney nickel (60%, aqueous),1.5 g of formamidine acetate and 120 ml of methanol are introduced in anautoclave equipped with gas introduction stirrer. The air is thendisplaced by nitrogen and then by hydrogen. The hydrogenation is carriedout at a pressure of 12 bar and a temperature of 80° C. Thehydrogenation time is 11/2 hours. 1-Chloro-3-aminobenzene, 99.4% pure(analysed by gas chromatography), is obtained in quantitative yield.

EXAMPLE 5

48.0 g of 1,2-dichloro-4-nitrobenzene, 2 g of Raney nickel (60%,aqueous), 1.5 g of formamidine acetate and 120 ml of methanol areintroduced in an autoclave equipped with gas introduction stirrer. Theair in the autoclave is then displaced by nitrogen and then by hydrogen.The hydrogenation is carried out at a pressure of 12 bar and atemperature of 80° C. The hydrogenation time is 1 hour.1,2-Dichloro-4-aminobenzene, 99.7% pure (analysed by gaschromatography), is obtained in quantitative yield.

EXAMPLE 6

48.0 g of 1,4-dichloro-2-nitrobenzene, 2 g of Raney nickel (60%,aqueous), 1.5 g of formamidine acetate and 120 ml of methanol areintroduced in an autoclave equipped with gas introduction stirrer. Theair in the autoclave is then displaced by nitrogen and then by hydrogen.The hydrogenation is carried out at a pressure of 12 bar and atemperature of 80° C. The hydrogenation time is 1 hour.1,4-Dichloro-2-aminobenzene, 99.6% pure (analysed by gaschromatography), is obtained in quantitative yield.

EXAMPLE 7

48.0 g of 1,2-dichloro-3-nitrobenzene, 2 g of Raney nickel (60%,aqueous), 1.5 g of formamidine acetate and 120 ml of methanol areintroduced in an autoclave equipped with gas introduction stirrer. Theair in the autoclave is then displaced by nitrogen and then by hydrogen.The hydrogenation is carried out at a pressure of 12 bar and atemperature of 80° C. The hydrogenation time is 1 hour.1,2-Dichloro-3-aminobenzene, 99.7% pure (analysed by gaschromatography), is obtained in quantitative yield.

EXAMPLE 8

50.5 g of 1-bromo-2-nitrobenzene, 2 g of Raney nickel (60%, aqueous),1.5 g of formamidine acetate and 120 ml of methanol are introduced in anautoclave equipped with gas introduction stirrer. The air in theautoclave is then displaced by nitrogen and then by hydrogen. Thehydrogenation is carried out at a pressure of 10 bar and a temperatureof 65° C. The hydrogenation time is 21/2 hours. 1-Bromo-2-aminobenzene,97.8% pure (analysed by gas chromatography), is obtained in quantitativeyield.

EXAMPLE 9

50.5 g of 1-bromo-3-nitrobenzene, 2 g of Raney nickel (60%, aqueous),1.5 g of formamidine acetate and 120 ml of methanol are introduced in anautoclave equipped with gas introduction stirrer. The air in theautoclave is then displaced by nitrogen and then by hydrogen. Thehydrogenation is carried out at a pressure of 10 bar and a temperatureof 65° C. The hydrogenation time is 2 hours. 1-Bromo-3-aminobenzene,98.7% pure (analysed by gas chromatography), is obtained in quantitativeyield.

EXAMPLE 10

40.8 g of 1-chloro-2,4-dinitrobenzene, 2 g of Raney nickel (60%,aqueous), 2.3 g of N,N'-dibutylformamidine acetate and 120 ml ofmethanol are introduced in an autoclave equipped with gas introductionstirrer. The air in the autoclave is then displaced by nitrogen and thenby hydrogen. The hydrogenation is carried out at a pressure of 10 barand a temperature of 60° C. The hydrogenation time is 11/4 hours.1-Chloro-2,4-diaminobenzene, 97% pure (analysed as1-Chloro-2,4-acetamidobenzene by liquid chromatography), is obtained inquantitative yield.

EXAMPLE 11

39.8 g of 1-chloro-2-nitrobenzene, 2 g of Raney nickel (60%, aqueous),1.5 g of formamidine acetate, 100 ml of toluene and 20 ml of methanolare introduced in an autoclave equipped with gas introduction stirrer.The air in the autoclave is then displaced by nitrogen and then byhydrogen. The hydrogenation is carried out at a pressure of 10 bar and atemperature of 90° C. The hydrogenation time is 4 hours.1-Chloro-2-aminobenzene, 99.9% pure (analysed by gas chromatography), isobtained in quantitative yield.

EXAMPLE 12

1.5 g of cyanamide, 1.5 g of acetic acid, 2 g of Raney nickel (60%,aqueous), and 120 ml of methanol are introduced in an autoclave equippedwith gas introduction stirrer. Under a hydrogen pressure of 4 bar and atemperature of 25° C., the cyanamide is hydrogenated quantitatively tothe formamidine acetate. 40.8 g of 1-chloro-2,4-dinitrobenzene are thenadded to the autoclave, and the hydrogenation is carried out at apressure of 10 bar and a temperature of 60° C. The hydrogenation time is1 hour. 1-Chloro-2,4-diaminobenzene, 97.5% pure (analysed as1-Chloro-2,4-acetamidobenzene by liquid chromatography), is obtained inquantitative yield.

EXAMPLE 13

3 g of dicyanodiamide, 3 g of acetic acid, 2 g of Raney nickel (60%,aqueous), and 120 ml of methanol are introduced in an autoclave equippedwith gas introduction stirrer. Under a hydrogen pressure of 4 bar and atemperature of 25° C., the dicyanodiamide is hydrogenated to theformamidine acetate. 40.8 g of 1-chloro-2,4-dinitrobenzene are thenadded to the autoclave, and the hydrogenation is carried out at apressure of 10 bar and a temperature of 60° C. The hydrogenation time is11/4 hours. 1-Chloro-2,4-diaminobenzene, 98% pure (analysed as1-Chloro-2,4-acetamidobenzene by liquid chromatography), is obtained inquantitative yield.

What is claimed is:
 1. A process for the preparation of halogenatedaromatic primary amines by catalytic hydrogenation of halogenatedaromatic nitro compounds in the presence of Raney nickel at a pressureof 0.1 to 100 bar and at a temperature of 30° to 150° C. in an inertsolvent and in the presence of an inhibitor against dehalogenation,wherein the inhibitor is a formamidine salt.
 2. A process according toclaim 1, wherein the formamidine salt is used in an amount of 0.1 to 30mol %, relative to the nitro compound.
 3. A process according to claim2, wherein the formamidine salt is used in an amount of 0.5 to 15 mol %.4. A process according to claim 1, wherein the formamidine salt conformsto the formula I ##STR3## in which R¹, R² and R³, independently of oneanother, are H, or linear or branched C₁ -C₁₂ alkyl, C₅ cycloalkyl or C₆cycloalkyl, C₆ -C₁₈ alkylcycloalkyl, C₆ C₁₀ cycloalkylalkyl, C₇ -C₁₈alkylcycloalkylalkyl, where the cycloalkyl contains 5 or 6 ring carbonatoms, C₆ -C₁₀ aryl, C₇ -C₁₈ alkaryl, C₇ -C₁₂ aralkyl or C₇ -C₁₈alkaralkyl or R¹ and R² together are tetramethylene or pentamethylene or3-oxa-1,5-pentylene, X is the anion of an acid, in particular of a C₁-C₁₈ mono- or -dicarboxylic acid, and n is 1 or
 2. 5. A processaccording to claim 4, wherein R¹, R² and R³, independently of oneanother, are H, or an aliphatic or cycloaliphatic group.
 6. A processaccording to claim 4, wherein in formula I R¹, R² and R³, independentlyof one another, are H or C₁ -C₆ alkyl.
 7. A process according to claim4, wherein in formula I R¹, R² and R³, independently of one another, areH, methyl or ethyl.
 8. A process according to claim 4, wherein informula I R¹, R² and R³, independently of one another, are each H.
 9. Aprocess according to claim 4, wherein n in formula I is
 1. 10. A processaccording to claim 4, wherein X in formula I as the anion of acarboxylic acid contains 1 to 8 carbon atoms.
 11. A process according toclaim 4, wherein X in formula I is the anion of an aliphatic C₁ -C₄mono- or -dicarboxylic acid.
 12. A process according to claim 11,wherein X in formula I is (COO)₂ ²⊖, HCOO.sup.⊖, CH₃ COO.sup.⊖, CH₃ CH₂COO.sup.⊖, CH₃ CH₂ CH₂ COO.sup.⊖ or CH₂ (COO)₂ ²⊖.
 13. A processaccording to claim 11, wherein X is CH₃ COO⁻.
 14. A process according toclaim 1, wherein the formamidine salt is formamidine acetate.
 15. Aprocess according to claim 1, wherein the Raney nickel is used in anamount of 0.5 to 20% by weight, relative to the nitro compound.
 16. Aprocess according to claim 1, wherein the solvent used is a C₁ -C₄alkanol by itself or in a mixture with water.
 17. A process according toclaim 16, wherein the solvent is methanol.
 18. A process according toclaim 1, wherein the temperature is 50° to 120° C.
 19. A processaccording to claim 1, wherein the pressure is 1 to 30 bar.
 20. A processaccording to claim 1, wherein the formamidine salt is prepared byhydrogenation of corresponding cyanamide in the presence of an acid insitu and the halogenated aromatic nitro compound is either initiallyintroduced as well in its total amount or partially introduced as welland the remainder is metered in later.